In order to understand the mechanism of action of cell surface active hormones, we propose to study the binding of insulin and glucagon to a viable target tissue, the hepatocyte. The responsiveness of isolated rat hepatocytes to these hormones and other bioregulators will be established employing stimulation of amino acid transport, synthesis, and adenylate cyclase as criteria. Insulin and glucagon receptors on the hepatocyte will be characterized in terms of the number of receptor sites, affinity and association and dissociation rates. The accumulation of a slowly dissociable peptide hormone binding fraction suggests that subsequent to initial occupancy, a change in receptor state occurs. This change in receptor binding properties will be correlated with cellular desensitization to further hormonal stimulation. Studies of hormone degradation by hepatocytes suggested that there may be some degree of cellular uptake of hormone. The roles played by changes in receptor state and degradation will be integrated into a study of cellular response to hormone binding.